Regulation of the levels of pyridoxal phosphate may play an important role in determining the metabolic capabilities of cells and tissues. For example, a number of enzymes involved in the intermediary metabolism of amino acids require pyridoxal phosphate. These enzymes are important in the quantitative disposition of amino acids and serve to connect carbohydrate and protein metabolism. In addition, roles for pyridoxal phosphate or pyridoxal phosphate-dependent enzymes have been proven or suggested in the central nervous system, during the cell cycle, in the production of pharmacologically active substances, in circadian rhythms, in stabilization of certain enzymes, and in the interaction of steroid hormones with their receptors. Thus, the three enzymes that are mainly responsible for the regulation of the amounts of pyridoxal phosphate in cells and tissues are extremely important. These enzymes are: pyridoxal phosphate phosphatase, pyridoxal kinase, and pyridoxine phosphate oxidase. We propose to study the activities of these enzymes under a variety of conditions so as to understand their roles during ontogeny, as a function of nutritional status, in response to hormonal alteration and drug administration, in regenerating liver, and during the cell cycle.